Many areas of biomedical research have benefited greatly from recent progress in mass spectrometry instrumentation and techniques. Time-of-flight mass spectrometry, in particular, has emerged as an important tool in molecular biology and biomedical research and medical diagnostics, due primarily to its ability to offer a superior combination of sensitivity, specificity, and throughput relative to other mass spectrometer platforms. However, by its nature, a time-of-flight mass spectrometer accepts sample ions for analysis on a pulsed basis. Therefore, when ions are produced continuously, such as in an ESI source, a majority of sample ions are typically lost between TOF pulses, which greatly limits the sensitivity that might otherwise be realized. Alternatively, when the production of ions is pulsed in synchronization with TOF analysis, as in MALDI, sample utilization is optimized, but throughput is often compromised significantly. The goal of this project is to develop and commercialize a new concept in the design of TOF mass spectrometers that overcomes the above limitations and promises improvements in sensitivity, and throughput by as much as a factor of 10 or more with improved resolving power. Briefly, the pulsed extraction region of a TOF mass spectrometer will incorporate a new ion optics design that provides a potential well for trapping ions between TOF extraction pulses. Such a potential well is created by the action of highly localized electric fields using specifically shaped electrodes combined with applied electric fields integrated into the structure of a TOF extraction region. This configuration provides ion trapping capability directly in the TOF extraction region without compromising any TOF performance parameter. Preliminary model calculations have been performed that suggest the feasibility of this novel approach. The objectives of this Phase 1 project are to design, build, and test several working prototypes of different designs to verify model calculations, and to evaluate practical feasibility in a commercially available ESI-TOF mass spectrometer. The expected increase in sensitivity and/or throughput will be greatly beneficial to many biomedical research and medical diagnostic areas, such as studies of low abundance, but critically important, constituents of various biological samples, molecular dynamics studies, high throughput screening applications and cell pathology.